Effectiveness and Safety of Acupotomy on Lumbar Spinal Stenosis: A Pragmatic, Pilot, Randomized Controlled Trial.

Purpose: In Korea, complex treatments such as acupotomy, acupuncture, and physical therapy are performed for lumbar spinal stenosis (LSS). Although there are reports of acupotomy as monotherapy or acupuncture treatment for LSS, pragmatic studies are lacking. Therefore, this study aimed to determine the effectiveness and safety of acupotomy for LSS to provide baseline evidence for a large-scale study. Materials and Methods: This pragmatic randomized controlled pilot study enrolled 34 participants and randomly assigned them to two groups (n=17/group). The intervention was conducted for 8 weeks. Acupotomy plus and usual care groups received acupuncture (17 acupoints) and interferential current therapy (ICT) twice weekly; however, the acupotomy plus group received an additional acupotomy (7 acupoints) for treatment of the usual care group. The primary outcome was measured using visual analog scales (VAS), and secondary outcomes were assessed using the self-rated walking distance, short-form McGill Pain Questionnaire (SF-MPQ), and the Oswestry Disability Index (ODI). Outcome measurements were conducted at baseline and 4, 8, and 12 weeks after the commencement of the intervention. Adverse events were assessed at each visit. Hematological and biochemical examinations were performed at screening and week 8. Results: Overall, 33 of the 34 participants completed the study, and one participant in the usual care group dropped out. In both groups, VAS scores at weeks 4, 8, and 12 significantly improved compared to baseline. Also, self-rated walking distance, SF-MPQ, and ODI scores were significantly improved at weeks 4, 8, and 12 than at baseline. However, there were no significant differences in the time-dependent and group-to-time interactions between the two groups. In addition, no severe adverse reactions were reported, and there were no significant differences in hematological and biochemical results. Conclusion: This study provides baseline data for large-scale studies on the effectiveness and safety of acupotomy in LSS. Clinical Trial Number: KCT0006234.

Efficacy and safety of thread embedding acupuncture for knee osteoarthritis: A randomized controlled pilot trial.

BACKGROUND: Thread embedding acupuncture (TEA) is a widely used clinical procedure for the treatment of musculoskeletal pain. However, few clinical studies have been conducted on the efficacy and safety of TEA for knee osteoarthritis (KOA), and data from randomized controlled trials are lacking. This randomized controlled pilot study aimed to assess the feasibility of conducting large-scale studies on the efficacy and safety of TEA for KOA. METHODS: Forty participants were included in the study and randomly divided into 2 groups (TEA and acupuncture) of 20 each. The intervention period was 6 weeks. The experimental group received TEA once a week (total of 6 sessions) on 14 defined knee areas, and the control group received acupuncture twice a week (total of 12 sessions) on 9 defined acupuncture points. The primary outcome measure was the visual analogue scale score, and the secondary outcome measures were the short-form McGill pain questionnaire, and Western Ontario and McMaster Universities Osteoarthritis Index scores. Participants were assessed prior to the intervention (baseline) and at 3, 6, and 10 weeks (4 weeks after the end of intervention). The adverse effects of TEA and acupuncture were documented. Hematological examination and biochemical tests were performed at the screening and at 6 weeks. RESULTS: Of the 40 participants, 37 completed the study and 3 participants dropped out. Both the TEA and acupuncture groups showed a significant improvement in the visual analogue scale, short-form McGill Pain Questionnaire, and Western Ontario and McMaster Universities Osteoarthritis Index scores in a time-dependent manner. However, there was no significant interaction between group and time. No serious adverse events were reported in the groups, and no clinically significant changes were observed in the hematological and biochemical parameters. CONCLUSION: This pilot study suggests that TEA is a safe and effective procedure for relieving pain in patients with KOA. The results of this study provide basic data and indicate the feasibility of large-scale clinical studies to evaluate the efficacy and safety of TEA for KOA.

Effectiveness and safety of acupotomy on lumbar spinal stenosis: A pragmatic randomized, controlled, pilot clinical trial: A study protocol.

INTRODUCTION: Lumbar spinal stenosis (LSS) is a pathological condition that causes a variety of neurological symptoms due to narrowing of the anatomical structures; usually, conservative treatment is recommended, rather than surgical treatment. Acupotomy combines conventional acupuncture with small scalpels; the procedure can be considered minimally invasive, and has recently received considerable attention in clinical practice. Still, there is a lack of data and randomized controlled trials regarding acupotomy related to LSS. Additional studies are necessary, considering the low methodological quality and small size of the study. METHODS AND ANALYSIS: This is a pragmatic, pilot, randomized controlled trial. The trial comprises 8 weeks of treatment, with 16 visits and a 4-week follow-up period. Forty participants diagnosed with LSS will be randomly assigned to either the experimental or control groups; both groups will receive acupuncture and interferential current therapy twice a week for 8 weeks, while the experimental group will receive an additional acupotomy intervention once a week for 8 weeks. The primary outcome will be assessed using the visual analog scale; the secondary outcome will be measured by self-rated walking distance, Oswestry Disability Index, and short-form McGill Pain Questionnaire. Measurements will be obtained prior to the start of the clinical trial, 4 weeks after the interventional procedure, 8 weeks after the procedure, and 4 weeks after the end of the interventional procedure. Blood tests and adverse reactions will be performed to ensure safety of the treatments. CONCLUSION: We expect that this study will provide basic data for future large-scale acupotomy studies regarding LSS.

Efficacy and safety of thread embedding acupuncture on knee osteoarthritis: A randomized, controlled, pilot clinical trial.

INTRODUCTION: Although there are various therapeutic methods for the treatment of knee osteoarthritis, each has its advantages and shortcomings, and a definitive treatment method is yet to be determined. This pilot study is designed to obtain basic data for a further large-scale trial as well as provide information about the feasibility of thread embedding acupuncture (TEA) with polydioxanone thread in knee osteoarthritis patients. METHODS AND ANALYSIS: This study is a clinical trial to evaluate the efficacy and safety of TEA for knee osteoarthritis. Forty participants will be recruited at the hospital and after randomization into 2 groups of 20 (experimental and control); they will be treated for 6 weeks. The experimental group will receive TEA treatment 6 times (1 time/week) in 6 weeks on 14 defined knee areas, and the control group, acupuncture treatments 12 times (2 times/week) in 6 weeks on 9 defined acupuncture points. The visual analogue scale (VAS) will be used for the primary efficacy assessment and Short-form McGill Pain Questionnaire (SF-MPQ), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) will be used for the secondary efficacy assessment. The follow-ups before clinical trial, 3 weeks after procedure, 6 weeks after procedure, and 4 weeks after the end of procedure will be done to compare the degree of pain with the control group, which received the acupuncture treatment. CONCLUSION: The trial based on this study will provide clinical information on the efficacy and safety of TEA treatment on knee osteoarthritis. TRIAL REGISTRATION NUMBER: KCT0004844.

Hepatoprotective Effect of Pericarpium zanthoxyli Extract Is Mediated via Antagonism of Oxidative Stress.

Pericarpium zanthoxyli has been extensively used in traditional Oriental medicine to treat gastric disorders and has anti-inflammatory and antioxidative activities. Therefore, the present study examined a possible hepatoprotective effect of a P. zanthoxyli extract (PZE) and investigated the underlying molecular mechanisms. We employed an in vitro model of arachidonic acid (AA) + iron-induced hepatocyte damage and an in vivo model of CCl4-induced liver injury to assess the effects of PZE and evaluated the relevant molecular targets using biochemical assays, flow cytometry analysis, Western blot, and histopathological analysis. The PZE inhibited AA + iron-induced hepatotoxicity in HepG2 cells, improved mitochondrial dysfunction, and reversed an increase in the cellular H2O2 production and a decrease in the reduced GSH levels induced by AA + iron. Treatment with either 30 or 100 µg/ml PZE significantly increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and the latter dose also increased the antioxidant response element- (ARE-) driven luciferase activity and enhanced the protein expressions of glutamate-cysteine ligase catalytic subunit and NAD(P)H:quinone oxidoreductase 1. In addition, treatment with 100 µg/ml PZE for 3 or 6 h increased the phosphorylation rates of Nrf2 and the extracellular signal-regulated kinase. In the in vivo experiment, oral treatment with both 100 and 300 mg/kg PZE inhibited the plasma aspartate aminotransferase activity, and the latter also inhibited the plasma alanine aminotransferase activity. In addition, both doses of PZE ameliorated the parenchymal degeneration and necrosis in the liver induced by CCl4 administration, which was associated with reduced expressions of cleaved caspase-3, cleaved poly (ADP-ribose) polymerase, nitrotyrosine, and 4-hydroxynonenal by PZE. These findings suggest that PZE has protective effects against hepatotoxicity both in vitro and in vivo, which are mainly mediated via its antioxidant activity.

Effects of Pelargonium sidoides and Coptis Rhizoma 2 : 1 Mixed Formula (PS + CR) on Ovalbumin-Induced Asthma in Mice.

Pelargonium sidoides (PS) is traditionally used to treat respiratory and gastrointestinal infections, dysmenorrhea, and hepatic disorders in South Africa. Coptis Rhizoma (CR) is used to treat gastroenteric disorders, cardiovascular diseases, and cancer in East Asia. In the present study, we intended to observe the possible beneficial antiasthma effects of PS and CR on the ovalbumin- (OVA-) induced asthma C57BL/6J mice. Asthma in mice was induced by OVA sensitization and subsequent boosting. PS + CR (300 and 1,000 mg/kg; PO) or dexamethasone (IP) was administered once a day for 16 days. The changes in the body weight and gains, lung weights and gross inspections, total and differential cell counts of leukocytes in bronchoalveolar lavage fluid (BALF), serum OVA-specific immunoglobulin E (OVA-sIgE) levels, interleukin-4 (IL-4) and IL-5 levels in BALF and lung tissue homogenate, and IL-4 and IL-5 mRNA levels in lung tissue homogenates were analyzed with lung histopathology: mean alveolar surface area (ASA), alveolar septal thickness, numbers of inflammatory cells, mast cells, and eosinophils infiltrated in the alveolar regions, respectively. Significant increases in lung weights, total and differential cell counts of leukocytes in BALF, serum OVA-sIgE levels, and IL-4 and IL-5 levels in BALF and lung tissue homogenate were observed in OVA control as compared to those of intact control. In addition, OVA control showed a significant decrease in mean ASA and increases in alveolar septal thickness, numbers of inflammatory cells, mast cells, and eosinophils infiltrated in alveolar regions. However, these allergic and inflammatory asthmatic changes were significantly inhibited by PS + CR in a dose-dependent manner. In this study, PS + CR showed dose-dependent beneficial effects on OVA-induced asthma in mice through anti-inflammatory and antiallergic activities. Therefore, it is expected that PS + CR have enough potential as a new therapeutic agent or as an ingredient of a medicinal agent for various allergic and inflammatory respiratory diseases including asthma.

Hemistepsin A alleviates liver fibrosis by inducing apoptosis of activated hepatic stellate cells via inhibition of nuclear factor-κB and Akt.

Hemistepsin A (HsA), isolated from Hemistepta lyrata (Bunge) Bunge, has the ability to ameliorate hepatitis in mice. However, the effects of H. lyrata and HsA on other types of liver disease have not been explored. In this report, we investigated the effects of H. lyrata and HsA on liver fibrosis and the underlying molecular mechanisms in activated hepatic stellate cells (HSCs). Based on cell viability-guided isolation, we found HsA was the major natural product responsible for H. lyrata-mediated cytotoxicity in LX-2 cells. HsA significantly decreased the viability of LX-2 cells and primary activated HSCs, increased the binding of Annexin V, and altered the expression of apoptosis-related proteins, suggesting that HsA induces apoptosis in activated HSCs. HsA reduced the phosphorylation of IKKε and the transactivation of nuclear factor-κB (NF-κB). Moreover, HsA decreased the phosphorylation of Akt and its downstream signaling molecules. Transfection experiments suggested that inhibition of NF-κB or Akt is essential for HsA-induced apoptosis of HSCs. In a CCl4-induced liver fibrosis model, HsA administration significantly decreased ALT and AST activities. Furthermore, HsA attenuated CCl4-mediated collagen deposits and profibrogenic genes expression in hepatic tissue. Thus, HsA may serve as a natural product for managing liver fibrosis through inhibition of NF-κB/Akt-dependent signaling.

Sipjeondaebo-tang Alleviates Oxidative Stress-Mediated Liver Injury through Activation of the CaMKK2-AMPK Signaling Pathway.

Sipjeondaebo-tang (SDT) is used frequently as a herbal prescription to treat deficiency syndromes in traditional Korean medicine. We investigated the hepatoprotective effects of SDT against oxidative stress and attempted to clarify the underlying molecular mechanisms. SDT pretreatment reduced arachidonic acid (AA) plus iron-mediated cytotoxicity in a concentration-dependent manner and prevented changes in apoptosis-related protein expression. In addition, SDT pretreatment significantly reduced glutathione depletion, hydrogen peroxide production, and mitochondrial dysfunction via treatment with AA plus iron. SDT increased the phosphorylation of AMP-activated protein kinase (AMPK) in accordance with the phosphorylation of Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2). Experiments using an AMPK chemical inhibitor (Compound C) or CaMKK2 chemical inhibitor (STO-609) suggested that the CaMKK2-AMPK signaling pathway contributes to SDT-mediated protection of mitochondria and cells. Moreover, administration of SDT for 4 consecutive days to mice significantly reduced the alanine aminotransferase and aspartate aminotransferase activities induced by carbon tetrachloride, and the numbers of degenerated hepatocytes, infiltrated inflammatory cells, nitrotyrosine-positive cells, and 4-hydroxynonenal-positive cells in liver tissue. Therefore, SDT protects hepatocytes from oxidative stress via CaMKK2-dependent AMPK activation and has the therapeutic potential to prevent or treat oxidative stress-related liver injury.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2.

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

Amelioration of inflammatory responses by Socheongryong-Tang, a traditional herbal medicine, in RAW 264.7 cells and rats.

Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 and prostaglandin E2 (PGE2) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation in vivo and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE2 and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE2, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms.

Efficacy and safety of combined treatment of miniscalpel acupuncture and non-steroidal anti-inflammatory drugs: an assessor-blinded randomized controlled pilot study.

BACKGROUND: Chronic neck pain is a common musculoskeletal disease during the lifespan of an individual. With an increase in dependence on computer technology, the prevalence of chronic neck pain is expected to rise and this can lead to socioeconomic problems. We have designed the current pilot study to evaluate the efficacy and safety of miniscalpel acupuncture treatment combined with non-steroidal anti-inflammatory drugs (NSAIDs) in patients with chronic neck pain. METHODS: This seven-week clinical trial has been designed as an assessor-blinded, randomized controlled trial with three parallel arms. Thirty-six patients will be recruited and randomly allocated to three treatment groups: miniscalpel acupuncture treatment; NSAIDs; and miniscalpel acupuncture treatment combined with NSAIDs. Patients in the miniscalpel acupuncture and combined treatment groups will receive three sessions of miniscalpel acupuncture over a three-week period. Patients in the NSAIDs and combined treatment groups will receive zaltoprofen (one oral tablet, three times a day for three weeks). Primary and secondary outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end point), and 7 (four weeks after treatment completion) using the visual analogue scale and the Neck Disability Index, EuroQol 5-dimension questionnaire, and Patients' Global Impression of Change scale, respectively. Adverse events will also be recorded. DISCUSSION: This pilot study will provide a basic foundation for a future large-scale trial as well as information about the feasibility of miniscalpel acupuncture treatment combined with NSAIDs for chronic neck pain. TRIAL REGISTRATION: Korean Clinical Research Information Service registry, KCT0002258 . Registered on 9 March 2017.

Tryptanthrin prevents oxidative stress-mediated apoptosis through AMP-activated protein kinase-dependent p38 mitogen-activated protein kinase activation.

Tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline) has been reported to have a variety of pharmacological activities. Present study investigated the cytoprotective effects of tryptanthrin on arachidonic acid (AA) + iron-mediated oxidative stress and the molecular mechanisms responsible. In HepG2 cells, pretreatment with tryptanthrin inhibited the cytotoxic effect of AA + iron in a concentration-dependent manner. In addition, tryptanthrin prevented the changes in the levels of apoptosis-related proteins, and attenuated reactive oxygen species production, glutathione depletion, and mitochondrial membrane impairment induced by AA + iron. Mechanistic investigations showed that tryptanthrin increased the phosphorylations of AMP-activated protein kinase (AMPK) and of p38 mitogen-activated protein kinase (p38). Furthermore, inhibition of AMPK or p38 reduced the ability of tryptanthrin to prevent AA + iron-induced cell death and mitochondrial dysfunction. Transfection experiments using AMPK mutants indicated that p38 phosphorylation by tryptanthrin was dependent on AMPK activation. In a phenylhydrazine-induced acute liver injury model, tryptanthrin decreased serum levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin in mice. Additionally, tryptanthrin reduced numbers of degenerating hepatocytes, infiltrating inflammatory cells, 4-hydroxynonenal-, and nitrotyrosine-positive cells in hepatic tissues. Thus, these results suggest tryptanthrin has therapeutic potential to protect cells from oxidative injury via AMPK-dependent p38 activation.

20S-Protopanaxadiol, an aglycosylated ginsenoside metabolite, induces hepatic stellate cell apoptosis through liver kinase B1-AMP-activated protein kinase activation.

BACKGROUND: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. METHODS: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides. H2O2 productions, glutathione contents, lactate dehydrogenase activities, mitochondrial membrane permeabilities, apoptotic cell subpopulations, caspase-3/-7 activities, transferase dUTP nick end labeling (TUNEL) staining, and immunoblot analysis were performed to elucidate the molecular mechanism responsible for ginsenoside-mediated cytotoxicity. Involvement of the AMP-activated protein kinase (AMPK)-related signaling pathway was examined using a chemical inhibitor and small interfering RNA (siRNA) transfection. RESULTS AND CONCLUSION: Of the 11 ginsenosides tested, 20S-protopanaxadiol (PPD) showed the most potent cytotoxic activity in both LX-2 cells and primary activated HSCs. Oxidative stress-mediated apoptosis induced by 20S-PPD was blocked by N-acetyl-l-cysteine pretreatment. In addition, 20S-PPD concentration-dependently increased the phosphorylation of AMPK, and compound C prevented 20S-PPD-induced cytotoxicity and mitochondrial dysfunction. Moreover, 20S-PPD increased the phosphorylation of liver kinase B1 (LKB1), an upstream kinase of AMPK. Likewise, transfection of LX-2 cells with LKB1 siRNA reduced the cytotoxic effect of 20S-PPD. Thus, 20S-PPD appears to induce HSC apoptosis by activating LKB1-AMPK and to be a therapeutic candidate for the prevention or treatment of liver fibrosis.

Activation of AMPK by Buddleja officinalis Maxim. Flower Extract Contributes to Protecting Hepatocytes from Oxidative Stress.

The Buddleja officinalis Maxim. flower is used in traditional Chinese and Korean medicine to treat inflammation, vascular diseases, headache, and stroke, as well as enhance liver function. This research investigated the effects of B. officinalis Maxim. flower extract (BFE) on hepatotoxicity. The cytoprotective effects and mechanism of BFE against severe mitochondrial dysfunction and H2O2 production in hepatotoxicity induced by coadministration of arachidonic acid (AA) and iron were observed in the HepG2 cell line. In addition, we performed blood biochemical, histopathological, and histomorphometric analyses of mice with carbon tetrachloride- (CCl4-) induced acute liver damage. BFE inhibited the AA + iron-mediated hepatotoxicity of HepG2 cells. Moreover, it inhibited mitochondrial dysfunction, H2O2 production, and glutathione depletion mediated by AA + iron in the same cells. Meanwhile, the cytoprotective effects of BFE against oxidative stress were associated with the activation of AMP-activated protein kinase (AMPK). In particular, based on the histopathological observations, BFE (30 and 100 mg/kg) showed clear hepatoprotective effects against CCl4-induced acute hepatic damage. Furthermore, it inhibited 4-hydroxynonenal and nitrotyrosine immunoreactivity in hepatocytes. These results provide evidence that BFE has beneficial hepatoprotective effects against hepatic damage via the activation of AMPK pathway. Accordingly, BFE may have therapeutic potential for diverse liver disorders.

Effects of spaced retrieval training (SRT) on cognitive function in Alzheimer's disease (AD) patients.

Among the non-pharmacological treatments of dementia, SRT is a good candidate strategy for rehabilitating the cognition of AD patients. This study investigates the efficacy of SRT on the cognition of AD patients with very mild to mild disease. We administered 24-session SRT to 13 very mild and 6 mild AD patients. To assess the change of the neuropsychological performance after SRT, we performed the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-K), the logical memory test (LMT), the Benton visual retention test A (BVRT-A), and the digit span test (DST). All tests were administered both before and after SRT. Retention spans were significantly increased up to 24 min after SRT in both very mild and mild AD patients (p<0.05), and this improvement was maintained for different sets of target information. Retainable words were also significantly increased after SRT in the very mild AD patients (p=0.007). However, we observed no changes in neuropsychological performance after SRT. Although we did not observe improvements in the neuropsychological tests following SRT, our results suggest that the treatment was an effective intervention for improving the memory of very mild to mild AD patients, and could potentially improve learning and retention outside the training session.